Clinical Trial of Efficacy Evaluation of Omega-3 with Risperidone on Seizures Frequency in Children with Refractory Epilepsy and Attention-Deficit/Hyperactivity Disorder.

Objectives
We aimed to answer the question whether or not previous antiepileptic drugs with combination of omega-3 and risperidone are more efficient than previous antiepileptic drugs with risperidone alone in decreasing of seizures monthly frequency of children with refractory epilepsy and attention-deficit/hyperactivity disorder (ADHD).


Material & Methods
In a randomized clinical trial (IRCT201604212639N18), participants referred to Pediatric Neurology Clinic of Shahid Sadoughi Hospital, Yazd, Iran from Jun 2015 were distributed randomly into two groups. In group I, one capsule of omega-3 daily and 0.5 mg of risperidone was divided into two doses with previous antiepileptic drugs and in group II, 0.5 mg of risperidone was divided into two doses with previous antiepileptic drugs were given. The drugs use was continued for three months and the children were followed up monthly for three consecutive months. Primary outcomes included seizure monthly frequency and good response (more than 50% of reduction in seizures monthly frequency). Secondary outcome was clinical side effects.


Results
Overall, 23 girls and 33 boys with mean age of 9.24+0.15 yr (29 children in omega-3 group and 27 children in control group) were evaluated. Omega-3 therapy was effective in decreasing of seizures monthly frequency (10.41±3.92 times vs. 17.01±4.98, P=0.03). Good response was seen in three children (11.1%) in control (95% confidence interval: 8%-22.8%) and in 9 children (31%) in omega-3 (95% CI: 47.83%-14.17%) group, which showed that omega-3 was more effective in seizure control. (P=0.001). Frequency of side effects was not different in the two groups (14.8 % in control vs. 20.7% in omega-3 groups, P=0.5).


Conclusion
Omega-3 might be used as an effective and safe drug in seizures control of children with refractory epilepsy and ADHD.


Material & Methods
In a randomized clinical trial (IRCT201604212639N18), participants referred to Pediatric Neurology Clinic of Shahid Sadoughi Hospital, Yazd, Iran from Jun 2015 were distributed randomly into two groups. In group I, one capsule of omega-3 daily and 0.5 mg of risperidone was divided into two doses with previous antiepileptic drugs and in group II, 0.5 mg of risperidone was divided into two doses with previous antiepileptic drugs were given. The drugs use was continued for three months and the children were followed up monthly for three consecutive months. Primary outcomes included seizure monthly frequency and good response (more than 50% of reduction in seizures monthly frequency). Secondary outcome was clinical side effects.

Conclusion
Omega-3 might be used as an effective and safe drug in seizures control of children with refractory epilepsy and ADHD.
Keywords: Epilepsy; Refractory epilepsy; Omega-3; ADHD ORIGINAL ARTICLE polyunsaturated fatty acids (15) were effective in reduction of severity or frequency of epileptic seizures. On the other hand, ratios of both blood omega-6 to omega-3 and arachidonic acid to eicosapentaenoic acid have been elevated in ADHD children (16). A clinical trial study showed that dietary supplementation with omega-3 fatty acids reduced ADHD symptoms (17).
Effect of omega-3 fatty acids on seizures control and omega-3 efficacy in reduction of ADHD symptoms have been assessed in other studies, but, we did not find any research which evaluated effectiveness of these fatty acids in children with combination of refractory epilepsy and ADHD. Therefore this clinical trial was conducted to answer the question whether or not previous antiepileptic drugs with combination of omega-3 and risperidone is more efficient than previous antiepileptic drugs with risperidone alone in decrease of seizures monthly frequency of children with refractory epilepsy and ADHD.

Materials & Methods
In a randomized single-blinded parallel group,

Results
Sixty-four children were enrolled, but three children did not return and five children stopped    Table 2 shows comparisons of the mean of age, weight, and seizure monthly frequency in the two groups and indicates that no statistically significant differences were seen from these viewpoints. Comparison of frequency of good response and monthly seizure frequency at the end of research period in both groups is shown in Table 3 which shows that omega-3 therapy was effective in decreasing of monthly frequency of seizures.
More than 50% of reduction in monthly seizure frequency (good response) occurred in 3 children  antiseizure effects of omega-3 may be due to increasing in seizure thresholds and lowering of inflammatory cytokines in epileptic patients (22) and by these mechanisms, omega-3 fatty acids can decrease seizure-associated cardiac arrhythmias and sudden cardiac deaths in epileptic patients (23).
In this study, omega-3 was safe and no lifethreatening clinical side effect was seen in children.

Author`s Contribution
Razieh Fallah: participated in design of the study, the acquisition, analysis, and interpretation of the data.
Shiva Eiliaei: participated in selection the subjects and taking informed consent, also statistical analysis of data.
Farzad Ferdosian: drafted and revised the manuscript and also supervised the final approval of the version to be published .
All authors agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.